Original Article. J Young Pharm, 2016; 8(3): A multifaceted peer reviewed journal in the field of Pharmacy

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1 J Young Pharm, 2016; 8(3): A multifaceted peer reviewed journal in the field of Pharmacy Original Article Impact of HIV associated neurocognitive disorders on activities of daily living and its association with depression in outdoor patients undergoing HAART Savita Saini *, Kiran Vijay Barar Department of Pharmacology, Sardar Patel Medical College, Bikaner, Rajasthan, INDIA. ABSTRACT Objective: The prime objective was to determine the impact of HIV-associated neurocognitive disorders on activities of daily living and its association with depression. Material & Methods: A prospective cohort study was conducted in 80 HIV positive patients, registered at ART Centre of PBM and AG Hospital, Bikaner. A test battery comprising of three scales was used i.e. International HIV Dementia Scale (IHDS), Activities of Daily Living(ADL) scale and PRIME-MD Patient Health Questionnaire(PHQ-9) to diagnose cognitive dysfunction, dependence in ADL and depression respectively. Results: The 32.50% (n=26) of the patients were diagnosed to have cognitive dysfunction (IHDS Score<10) while remaining 67.50% (n=54) of the patients were normal (IHDS Score>10). Out of these cognitively impaired patients, n=2 patients were found to be dependent in >2 ADL while remaining patients were able to perform their ADL independently. No significant association was found between depression and cognitive dysfunction. Conclusion: Patients having score of <10 on IHDS were further classified on the basis of dependence in ADL. The patients having high degree of depressive symptoms were more likely to have cognitive dysfunction but the results were not significant. Key words: HIV-associated neurocognitive disorder, Activities of daily living (ADL) scale, Patient health questionnaire (PHQ), International HIV dementia scale (IHDS), Asymptomatic neurocognitive impairment, Mild neurocognitive disorder, HIV associated dementia. Correspondence : Dr. Savita Saini, Professor and Head, Assistant Professor, Department of Pharmacology, C-21, Gyansarovar colony, Kota, Rajasthan, INDIA. Phone no: drsavitasaini04@gmail.com DOI: /jyp PICTORIAL ABSTRACT INTRODUCTION The HIV infection has been declared as one of the worst pandemic, which is often associated with neurocognitive and psychological impairment. The neurocognitive complications associated with HIV have recently been characterized as HIV-associated neurocognitive disorders (HAND). HAND defines three categories of dysfunction: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD). 1 Since the introduction of highly active antiretroviral therapy (HAART), the incidence of severe forms of HAND has declined significantly, whereas the prevalence of the milder forms has increased. 2,3 There is clinical significance of identifying the milder forms of HAND, as they can have a significant impact on the lives of people living with HIV. They have been shown to interfere with medication adherence, workplace performance, driving and ability to carry out tasks independently. 4,5,6 Major depressive disorder (MDD) is the most common neuropsychiatric symptom associated with HIV. MDD may share similar pathological features (e.g. frontostriatal circuits) to HIV infection and has been indepen dently associated with subtle cognitive decline in areas including attention, psychomotor speed, learning and memory, and executive functioning. Despite the similar underlying neural abnormalities, most studies have failed to find synergistic effects of depression and HIV infection on cognition. 7 The neuropsychological impairment among HIV-positive patients remains largely unrecognized because it is not routinely screened for, despite this recommendation in HIV treatment guidelines. Early and periodical neuro psychological screening of HIV positive asymptomatic individuals is a must in future to spot the neurocognitive deficits at an early stage. 8 MATERIAL AND METHODS Study design This was a prospective cohort study undertaken between Oct.2011 and Sept.2012 in 80 HIV/AIDS patients undergoing antiretroviral treatment. All the participants were registered with the ART Centre of PBM and AG Hospital, Bikaner, Rajasthan, India. Ethical considerations The study obtained ethical approval from the Ethical Committee of Sardar Patel Medical College, Bikaner. Study participants were invited to consent after being provided with adequate information about the study. To be eligible for inclusion in this study, following criteria were used for the participants- HIV positive patients on stabilized HAART for more than 6 weeks Men/women between the age years Ambulatory patients with CD4 count above 200 cells/mm 3 Ability to comprehend study procedures Journal of Young Pharmacists, Vol 8, Issue 3, Jul-Sep,

2 Seriously ill patients, pregnant women, patients having severe psychiatric disorder or any substance abuse were excluded from the study. Data collection tools All the participants underwent neurocognitive examination, assessment of depression and activities of daily living. The tools included a sociodemographic questionnaire, the International HIV Dementia Scale (IHDS), Activities of Daily Living (ADL) scale and PRIME-MD Patient Health Questionnaire (PHQ-9). According to modified updated American Academy of Neurology (AAN) criteria, patients with HAND are classified on the basis of neurocognitive impairment and severity of dependence in activities of daily living (ADL). To assess neurocognitive impairment we used IHDS while dependence in ADL was assessed by ADL scale. International HIV Dementia Scale The IHDS is a screening measure of neurocognitive impairment that assesses for memory impairment, motor and psychomotor speed. It can be used in a clinic setting, does not require one to be proficient in English and is brief and inexpensive. Here a cut-off score of <10 was taken to screen dementia cases. 9 Activities of daily living scale This questionnaire was selected for its wide use and demonstrated validity in studies of medically ill and dementia population, including HIV. It includes 2 scales namely Katz basic activities of daily living scale and Lawton-Brody Instrumental activities of daily living scale. 10,11 It is a 14-item scale that measures physical self-maintenance activities and instrumental activities of daily living. Patients were classified as ADL dependent if they reported decline in two or more ADL. PRIME-MD Patient Health Questionnaire (PHQ-9) for endogenous depression The PHQ-9 follows the Diagnostic and Statistical Manual-IV (DSM-IV) Criteria for screening patients for current depression. If 5 or more of the 9 symptoms are present and one of the symptoms is sadness/ hopelessness or anhedonia, then a diagnosis of major depressive disorder is supported. 12,13 Statistical Analysis Means and Standard Deviations (SD) were calculated for continuous variables. To analyse the association between the various factors and cognitive dysfunction, chi square test was employed. The p value of less Table 1: Socio-demographic characteristics of participants (N=80) Parameter Number of participants (%) Age (in years) Gender Male Female Marital status Married Single Widow/Divorced Educational status Illiterate Primary school Secondary school College & above 13(16) 43(54) 24(30) 45(56) 35(44) 58(73) 4(5) 18(22) 41(51) 25(31) 10(13) 4(5) Table 2: Classification of HIV patients based on neurocognitive tests Nature of neurocognitive dysfunction No. of patients (%) HIV-Associated Dementia (HAD) Nil Mild Neurocognitive Disorder (MND) 2 (2.5) Asymptomatic Neurocognitive Impairment (ANI) 24 (30) No cognitive impairment 54 (67.5) Table 3: Depressive symptom and cognitive dysfunction Depressive symptom Cognitive dysfunction No cognitive dysfunction χ 2 p value Minimal (1-4) 17 (65.38) 40 (74.07) >0.05 Mild (5-9) 5 (19.23) 10 (18.52) >0.05 Moderate (10-14) 3 (11.54) 4 (7.41) >0.05 Moderately severe (15-19) 1 (3.84) Nil - - Severe (20-27) Nil Nil Journal of Young Pharmacists, Vol 8, Issue 3, Jul-Sep, 2016

3 Figure 1: Distribution of patients according to IHDS score. Figure 2: Distribution of Patients according to ADL score. than 0.05 was considered as statistically significant. All statistical analysis was done by using INDOSTAT software. RESULTS Of the 80 study participants, 45 were males (56%) and 35 were females (44%). The socio-demographic characteristics of the participants are presented in Table 1. In present study, using a cut-off score of 10 or less on the IHDS, patients were classified as having cognitive dysfunction and normal cognitive function. Out of total 80 HIV-positive patients, 26 patients (32.50%) had scored <10 on IHDS while remaining 54 patients (67.50%) scored >10 (See Figure 1). Further classification of cognitively impaired patients was done on the basis of dependence in ADL. The 2.50% (n=2) of the patients were found to be dependent in >2 ADL while the 97.50% (n=78) of the patients were able to perform their ADL independently i.e. ADL independent (See Figure 2). Classification of HAND according to modified updated American Academy of Neurology (AAN) criteria Patients who were found to be dependent in ADL and had scored <10 on the IHDS were classified under mild neurocognitive disorder (MND) category of HAND whereas the patients who were ADL independent and had a score of <10 on IHDS were categorised under asymptomatic Journal of Young Pharmacists, Vol 8, Issue 3, Jul-Sep,

4 neurocognitive impairment (ANI) category. The most severe form of HAND i.e. HAD was not observed in any of the subjects (See Table 2). PRIME-MD PHQ-9 scoring for endogenous depression The patients having high degree of depressive symptoms were more likely to have cognitive dysfunction but the results were not significant (p>0.05) (See Table 3). DISCUSSION In today s world, HIV/AIDS has poorly affected the vast majority of population and it still remains the major health burden across the world. With the prevalence of milder forms of HAND increasing and limited resources available for formal neuropsychological examinations, there is a critical need to be able to screen people with neurocognitive disorders. Asymptomatic Neurocognitive Impairment (ANI) is very common in AIDS patients and it was observed in 30% of our study subjects. All of these subjects were ADL independent. This finding is an agreement of finding of Lawler K et al, in which majority of the patients having cognitive dysfunction were asymptomatic. 14 HIV-associated Mild Neurocognitive Disorder (MND) constituted 2.5% of our study population who were found to be ADL dependent. Similar finding was observed in a previous study by Muniyandi K et al. 15 None of the patients had HAD which was in concordance with two prospective studies from India which also reported low incidence of HAD (1 to 2%). 16,17 One of the factors discussed in relation to cognitive dysfunction in HIV positive individuals is co-morbid depression. In concordance with previous studies 18,7 the present study also did not observed significant association between depression and cognitive dysfunction. CONCLUSION To conclude, the neuropsychological impairment among HIV positive patients on ARV therapy leads to a reduction in the quality of life and the patients having high degree of depressive symptoms are more likely to have cognitive dysfunction. It is an important challenge due to the high prevalence of HAND and its concomitant consequences in relation to morbidity and mortality. The presence of mild neurocognitive disorder in HIV is predictive of HAD, the most severe form of HAND. Therefore, early and periodical neuropsychological screening of HIV positive individuals is a must in future, to spot the neurocognitive deficits at an early stage. ACKNOWLEDGEMENT The authors are thankful to the entire faculty of the ART Center and Medicine Department, PBM and AG Hospital, Bikaner, Rajasthan (India), for their cooperation and support during this study. CONFLICT OF INTEREST The author have no conflict of interest to declare. ABBREVIATIONS USED HIV: Human immunodeficiency virus; AIDS: Acquired immunodeficiency syndrome; ART: Antiretroviral treatment; HAART: Highly active antiretroviral therapy; IHDS: International HIV dementia scale; ADL: Activities of daily living; PHQ: Patient health questionnaire; HAND: HIV associated neurocognitive disorder; ANI: Asymptomatic neurocognitive impairment; MND: Mild neurocognitive disorder; HAD: HIV associated dementia; MDD: Major depressive disorder; AAN: American academy of neurology; DSM: Diagnostic and statistical manual; SD: Standard deviation. ABOUT AUTHORS Dr. Savita Saini: Is Assistant professor at the department of Pharmacology, Sardar Patel Medical College, Bikaner, Rajasthan (India). She has completed MD (Pharmacology) in 2013 at S.P.Medical college, Bikaner. She has nine research publications. Dr. Kiran Vijay Barar: Is Senior Professor at the Department of Pharmacology, S.P.Medical College, Bikaner, Rajasthan, India. She is also serving as Honorary Professor at Albert Schiwtzer International University (ASIU), Geneva, Switzerland since yr She has published about 75 papers and has been an Editor, Reviewer and Writer/Columnist. She has been a Meritorious (Gold Medalist) throughout, Winner of various Distinctions, Awards and Prizes during her whole academic career and she has been recipient of National Merit Scholarship for four years ( ). She has served as Resource-Person/Moderator in various teaching programs/cme/group-discussions and also Deliberated Lead-Lectures in Neurodegenerative/Alzheimer s Disease(s), Biopharmaceuticals/ Biosimilars, Monoclonal-Antibodies etc. Recently, on Drug Regulatory Affairs and Obesity, Dr.Kiran deliberated lectures at Singapore and Las Vegas as Invited Speaker, Which have been published in Obesity journal in REFERENCES 1. Antinori A, Arendt G, Becker JT. Updated research nosology for HIV-associated neurocognitive disorders. 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